Using gadolinium to identify stretch-activated channels: technical considerations

• Published in: American Journal of Physiology: Cell Physiology 1998-08, Vol.275 (2), p.C619-C621
• Main Authors: Caldwell, Ray A, Clemo, Henry F, Baumgarten, Clive M
• Format: Article
• Language: English
• ISSN: 0363-6143; 1522-1563
• DOI: 10.1152/ajpcell.1998.275.2.c619

Departments of 1  Physiology and 2  Medicine, Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia 23298 Gadolinium (Gd 3+ ) blocks cation-selective stretch-activated ion channels (SACs) and thereby inhibits a variety of physiological and pathophysiological processes. Gd 3+ sensitivity has become a simple and widely used method for detecting the involvement of SACs, and, conversely, Gd 3+ insensitivity has been used to infer that processes are not dependent on SACs. The limitations of this approach are not adequately appreciated, however. Avid binding of Gd 3+ to anions commonly present in physiological salt solutions and culture media, including phosphate- and bicarbonate-buffered solutions and EGTA in intracellular solutions, often is not taken into account. Failure to detect an effect of Gd 3+ in such solutions may reflect the vanishingly low concentrations of free Gd 3+ rather than the lack of a role for SACs. Moreover, certain SACs are insensitive to Gd 3+ , and Gd 3+ also blocks other ion channels. Gd 3+ remains a useful tool for studying SACs, but appropriate care must be taken in experimental design and interpretation to avoid both false negative and false positive conclusions. mechanosensitive channels; mechanoelectrical feedback; lanthanides; chelation